Hippophae Rhamnoides‐derived Phytomedicine Nano‐System Modulates Bax/Fas Pathways to Reduce Proliferation in Triple‐Negative Breast Cancer

Triple-negative breast cancer (TNBC) is the most common primary tumor of the breast with limited effectual drug availability. Therefore, the aim of the study is to develop an innovative phyto-nanomedicine (PNM) to cure TNBC with the least genotoxicity. Hereinafter, the sea buckthorn' extracted polyphenols (SBP), combine with metformin (MET), are synthesized as a novel PNM to evaluate its anti-tumor properties, effectiveness, and mechanism of action in TNBC in vitro and in vivo models. The SBP exhibits 16 new kinds of polyphenols that are been reported earlier which regulated cell development, proliferation, and programmed cell death (PCD) effectively. SBP-MET PNM inhibits MDA-MB-231 (47%), MDA-MB-436 (46%), and 4T1 (46%) cell proliferation but does not affect L929 normal murine cell development and successfully induce PCD (73.19%) in MDA-MB-231 cells. Mechanistically, in vivo SBP-MET proteome expression profiling reveals upregulation of proapoptotic Bax protein and activation of Fas signaling pathways convince downstream Daxx and FADD proteins, which further triggers Caspase-3 that prompts apoptosis in human TNBC cells by cleaving PARP-1 protein. Current findings establish innovative highly biocompatible phyto-nanomedicine that has significant potential to inhibit TNBC cell growth and induce regulated cell death (RCD) in vivo model, thereby opening a new arena for TNBC therapy.